A. OBJECTIVES AND GOALS. The development and application of biomarkers in neurodegenerative diseases has become increasingly important to clinical practice, epidemiology and therapeutic trials. While substantial progress has been made at the basic science level in understanding the pathophysiology and development of animal models of HIV-D, there are significant limitations in our current ability to predict disease onset, to give definitive diagnoses, to measure disease progression and to detect accurately the effects of therapeutic intervention. Thus the development of objective biomarkers is critical to further our progress in this field. Realizing the potential importance of biomarkers, the Food and Drug Administration is making a major effort to bring biomarkers into the mainstream of drug discovery (1). The objectives of the Core are: 1. To assist in the development and monitoring of surrogate markers for HIV-D. 2. To provide mentorship and consultation for Neuro-AIDS researchers in the development of clinically useful surrogate markers for HIV-D and to validate these as associative, predictive markers, and as longitudinal markers of therapeutic effectiveness. This Core will interact extensively with the Clinical Outcomes Core (using the characterized samples derived from that Core), the Education and Skills Development Core (to disseminate information about the newly developed surrogate markers, and to assist with skill development in their application), and with the Therapeutics Core (to validate these markers in animal models). The statistical resources of the Clinical Outcomes Core will be essential for the interpretation of the clinical utility of markers derived from this core. Further details of the interactions are provided in individual Cores, and the overall Outline. This Core will provide a valuable resource to JHU investigators, and to the global Neuro-AIDS community. There is no similar systematic attempt to develop a series of clinically useful surrogate markers, so this Core will have a major impact on the field.